This application supports our continued participation as a Clinical Center in the NIH Exploratory Trials in Parkinson's Disease (NET-PD). Neuroprotection for Parkinson's disease, or disease modifying therapy, has been an elusive target. Based on prior NET-PD coordinated studies of creatine in patients with early Parkinsons disease, the NET-PD LS-1 study was designed as a large, randomized, multi-center clinical trial of creatine 5gm bid vs. placebo in 1720 patients with Parkinsons disease, with intent to follow these patients in active treatment for at least five years. The end point will be progression of Parkinson's symptoms and measures of disability as documented by a global statistical test. At the combined site of Brigham and Women's Hospital and Massachusetts General Hospital, we received IRB approval in October 2006 and rapidly enrolled 37 subjects into the LS-1 study (see Inclusion Enrollment Report). We have had excellent retention (92%) in the study by maintaining contact with subjects outside of the planned study visits. We have had five patients discontinue study drug but agree to continue to be observed for the remainder of the study. One subject is withdrawing from the study permanently due to disease progression. One patient had a possible allergic reaction, one had colon cancer, one developed metastatic lung cancer and is undergoing chemotherapy, one had palpitations which she felt were related to study drug and one became a living related kidney donor (and suspended study drug at the recommendation of her treating physicians). Overall our subjects are pleased to be participating in this study and we have had no difficulties with follow-up due to the long duration of the study. We are enthusiastic about continuing to collaborate with the other NET-PD centers (including the Coordination and Statistical Centers) towards the goal of successfully completing the current trials. We are also eager to participate in any future trials administered through the NET-PD infrastructure.